AIM: To explore the relationship between small intestinal motility and small intestinal bacteria overgrowth (SIBO) in Nonalcoholic steatohepatitis (NASH), and to investigate the effect of SIBO on the pathogenesis of NASH in rats. The effect of cidomycin in alleviating severity of NASH is also studied. METHODS:Forty eight rats were randomly divided into NASH group (n = 16), cidomycin group (n = 16) and control group (n = 16). Then each group were subdivided into small intestinal motility group (n = 8), bacteria group (n = 8) respectively. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (E. coli ) and anaerobes (Lactobacilli). Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT, AST levels were detected to evaluate the severity of hepatitis. RESULTS:Small intestinal transit was inhibited in NASH group (P < 0.01). Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group (P < 0.01). High fat diet resulted in quantitative alterations in the aerobes (E. coli ) but not in the anoerobics (Lactobacill). There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group (1.70 ± 0.12 log10 (CFU/g) vs 1.28 ± 0.07 log10 (CFU/g), P < 0.01). TNF-α concentration was significantly higher in NASH group than in control group (1.13 ± 0.15 mmol/L vs 0.57 ± 0.09 mmol/L, P < 0.01). TNF-α concentration was lower in cidomycin group than in NASH group (0.63 ± 0.09 mmol/L vs 1.13 ± 0.15 mmol/L, P < 0.01). Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-α levels of NASH rats.CONCLUSION: SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash. And treatment with cidomycin by mouth can alleviate the severity of NASH.
Background Interleukin‐1β (IL‐1B) has been recognized as a pro‐inflammatory cytokine and associated with tumorigenesis. We aimed to evaluate the contribution of IL‐1B polymorphisms to the susceptibility of cervical cancer in Chinese Uygur population. Methods Seven variants were genotyped by Agena MassARRAY platform in 267 cervical cancer patients and 302 healthy controls. Allelic, genotypic, and haplotypic association analyses adjusted for age were investigated using odds ratios (OR) and 95% confidence intervals (CI). GEPIA and UALCAN databases were used to evaluate expression and prognostic of IL‐1B gene in cervical cancer. Results Our result revealed IL‐1B rs1143627‐AA (OR = 1.98, p = 0.029) and rs16944‐GG (OR = 2.01, p = 0.025) was associated with an increased risk of cervical cancer. Besides, we also found two protective single nucleotide polymorphisms (SNPs) rs3136558 (OR = 0.63, p = 0.011) and rs1143630 (OR = 0.63, p = 0.019). Haplotype ″TGA″ in the block (rs1143630, rs1143627, and rs16944) significantly decreased the susceptibility of cervical cancer (OR = 0.53, p = 0.0007). IL‐1B mRNA level was up‐regulated in the cervical cancer patients, which was related with poor prognosis in silico. Conclusions For the first time, our results provide evidence on polymorphism of IL‐1B gene associated with cervical cancer risk in Chinese Uygur population.
SIRT1 is a pleiotropic protein that plays critical and multifunctional roles in metabolism, senescence, longevity, stress-responses, and cancer, and has become an important therapeutic target across a range of diseases. Recent research demonstrated that SIRT1 pre-mRNA undergoes alternative splicing to produce different isoforms, such as SIRT1 full-length and SIRT1-ΔExon8 variants. Previous studies revealed these SIRT1 mRNA splice variants convey different characteristics and functions to the protein, which may in turn explain the multifunctional roles of SIRT1. However, the mechanisms underlying the regulation of SIRT1 alternative splicing remain to be elucidated. Our objective is to search for new pathways that regulate of SIRT1 alternative splicing. Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances: HuR increased SIRT1-ΔExon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-ΔExon8 mRNA levels. This study provides novel insight into how the alternative splicing of SIRT1 pre-mRNA is regulated, which has fundamental implications for understanding the critical and multifunctional roles of SIRT1.
Macrophage apoptosis is a prominent characteristic of advanced atherosclerotic plaques and leads to plaque destabilization. Certain studies have confirmed that influenza virus A (IVA) infection is related to acute myocardial infarction (AMI). However, it remains unknown as to whether this phenomenon is associated with Toll-like receptor (TLR)7, since single-stranded RNA (ssRNA) of IVA is a natural ligand of TLR7. Thus, in the present study, THP-1‑derived macrophages were infected with IVA or treated with imiquimod (IMQ) in the presence or absence of pre-treatment with oxidized low-density lipoprotein (oxLDL). The macrophages were pre-treated with oxLDL (5 µg/ml) for 24 h to mimic high lipid conditions. Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-y-1)‑2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. Our results revealed that TLR7 played an important role in macrophage apoptosis and cytokine secretion. Both IVA infection and IMQ treatment increased TLR7 expression, as well as the secretion of pro-inflammatory cytokines [interleukin (IL)-6, monocyte chemotactic protein (MCP)-1] and apoptosis. However, this increase in cytokine secretion occurred independently of cell apoptosis. oxLDL had potential synergistic pro-apoptotic effects combined with TLR7 activation. To determine whether endoplasmic reticulum (ER) stress plays a role in cell apoptosis, the mRNA and protein expression of known markers of ER stress [glucose-regulated protein (GRP)78 and C/EBP homologous protein (CHOP)] was detected by reverse transcription PCR (RT-PCR), quantitative reverse transcription PCR (qRT-PCR) and western blot analysis. Our results revealed that apoptosis aggravated ER stress, as shown by the overexpression of the pro-apoptotic sensor, CHOP. In conclusion, our study demonstrates the converging role of oxLDL pre-treatment, IVA infection and IMQ in ER stress-induced cell apoptosis.
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